DESCRIPTION: (Verbatim from application) African American women are more obese and insulin resistant than Caucasian women. This research is designed to determine whether overweight African American women respond differently to hypocaloric weight loss (WL) or aerobic exercise plus weight loss (AEX+WL) than do Caucasian women. The hypothesis is that ethnic differences (African American vs. Caucasian) in the mechanisms by which WL affects insulin sensitivity in overweight, insulin resistant African American postmenopausal women requires that the WL be accompanied by AEX in African American women to improve insulin sensitivity. Specific aims determine 1) the race effects of WL vs. AEX+WL on insulin action on glucose and fat metabolism in African American compared to Caucasian women by assessing insulin sensitivity (EC50), and FFA suppression during hyperinsulinemia; and 2) the cellular mechanisms by which the addition of AEX to WL affects insulin sensitivity in African American compared to Caucasian women by ascertaining the effects of WL vs. AEX+WL on proteins affecting insulin action (GLUT4, IRS 1 and Pl-3 kinase) in skeletal muscle, and insulin suppression of lipolysis in adipocytes. We will study healthy, overweight (Body Mass Index, 27-35 kg/rn2) 50-60 year old postmenopausal African American and Caucasian women. Metabolic studies will be performed before and after either hypocaloric weight loss treatment (n=30 per race) or aerobic exercise training plus weight loss (n=30 per race). Insulin sensitivity and free fatty acid concentrations will be determined during a 3-step hyperinsulinemic-euglycemic clamp. We will measure total body fat (DXA scans), visceral fat and mid-thigh low density lean tissue (CT scans), glucose and insulin responses during an oral glucose tolerance test, skeletal muscle GLUT4, IRS 1, Pl 3-kinase, and insulin suppression of lipolysis in adipocytes. These findings may provide a rationale for targeting specific populations of women who might improve glucose and fat metabolism more from the addition of exercise to hypocaloric weight loss than weight loss alone.